PRESENTED BYSHWETA PARIK
M.Sc (I sem)
1.Aliphatic Nucleophilic Substitution and types
2.Mechanisms- introduction
3.The SN2 Mechanism
4.Evidences for the SN2 mechanism:
5.The SN1 Mechanism
6.Evidences for the SN1 Mechanism
7.THE SET Mechanism (single-electron
transfer).
8.The SNi Mechanism
9.Mixed SN1 AND SN2 Mechanism
10.Nucleophilic Substitution at an Allylic
Carbon
11.Nucleophilic Substitution at an Aliphatic
Trigonal
12.Carbon Nucleophilic Substitution at a Vinylic
Carbon
ALIPHATIC
NUCLEOPHILIC
SUBSTITUTION
SUBSTITUTION• replacement of an atom or group of
atom by any other atom or group of
atom.
NUCLEOPHILE At least one unshared pair of
electron
 Lewis base
 Attracted towards positively
charged species.
 May be neutral or negatively
charged.
 Example: Cl¯, Br¯, I¯, CN¯, OH¯,NH₃,
RNH₂, H₂O, ROH, etc.
General reactionR- X + Y:
substrate

nucleophile
R-Y + X:
substituted
product
Leaving
group
Nucleophile Y: may be neutral or negatively
charged.
Substrate may be neutral or positively
charged.
SN2
MECHANISM
 SN2 stands for
substitution nucleophilic
bimolecular.
BACK SIDE ATTACK
SINGLE STEP.
Direct displacement.
NO INTERMEDIATE
FORMATION
INVERSION OF
CONFIGURATION
The energy necessary to
break the C-L bond is
supplied by simultaneous
formation of the C-Nu
bond.
GENERALLY YIELD SINGLE
PRODUCT
Evidences for the SN2 mechanism:
1.Kinetics:
• rate expression,
Rate=
k[substrate][nucleophile]
• If a large excess of
nucleophile is present (i.e.
solvolysis) –
Rate= k [substrate]
such kinetics are called
pseudo-first order.
2. Stereochemistry:
3. No substitution at
bridgehead carbon
• Not be able to react by this
mechanism, since the nucleophile
cannot approach from the rear
• REQUIREMENT FOR SN2:
• SN2 mechanism requires the
backside attack by the nucleophile,
inversion of configuration and co
planarity of three no-reacting
groups in the transition state .
• REASON: prevented at the bridge
head carbons due to rigid cage like
structures
SN1
MECHANISM
SN1 mechanism (substitution
nucleophilic unimolecular)
TWO STEP PROCESS
The first step is a slow
ionization of the substrate and
is the rate-determining step
The second is a rapid
reaction between the
intermediate carbonation and
the nucleophile
The ionization of a leaving
group to form the carbocation
is always assisted by the
solvent, since the energy
necessary to break the bond is
largely recovered by solvation
of CATION and of LEAVING
GROUP.
EVIDENCES FOR THE SN1 MECHANISM:
1. kinetics
• first-order reaction
following the rate law:
RATE= k [RX]
• solvent is necessary to
assist in the process of
ionization, it does not enter
the rate expression,
because it is present in
large excess.
2. STEREOCHEMISTRY
 The stereo chemical
evidence for the SN1
mechanism is less clearcut than it is for the SN2
mechanism.
 First-order substitutions
do give complete
racemisation, many
others do not. Typically
there is 5–20% inversion.
• Some of the products
are not formed from
free carbocations but
rather from ion pairs.
• Role of ion pair:


•
Here is an intimate, contact, or tight ion pair; a loose or solvent-separated ion pair
and the dissociated ions (each surrounded by molecules of solvent) are formed.
The reaction products can result from attack by the nucleophile at any stage.
Nucleophilic attack by a solvent molecule on tight ion pair thus leads to inversion.
Attack on solvent separated ion pair leads to racemisation.
3. Formation of rearranged products:
THE SET MECHANISM (singleelectron transfer).
4. NO substitution at
bridgehead carbons
• Not be able to react by this
mechanism, since the nucleophile
• REQUIREMENT:
SN1 proceed through carbocations
which must be planar.
• REASON:
Because of rigid cage like structure,
bridgehead carbon atom cannot
assume planarity, hence
heterolysis leading to formation
of carbocation is prevented.
• In some nucleophilic reaction, sn1 is
highly probable.
• Esr detection of intermediate- free
radicals are involved.
• Carbocation- good electron
acceptor
• Nucleophile- good electron donor.
• Mechanism- SET mechanism. For
example, the reaction between the
triphenylmethyl cation and tbutoxide ion:•
Ph₃C⁺ + t-BuO¯
Ph₃C° + t-BuO°
t-BuOCPh₃
Mixed SN1 AND SN2 MECHANISM:• Some reactions of a given
substrate under a given set of
conditions display all the
characteristics of –
•
RX
•
SN1
IN BETWEENTWO THEORIES
intermediate
behaviour
•
•
mechanism that is neither ‘‘pure’’ SN1 nor
‘‘pure’’ SN2, but some ‘‘in-between’’ type.
all SN1 and SN2 reactions can be
accommodated by one basic mechanism
(the ion-pair mechanism).
K2
2: simultaneous operation:
•
: INTERMEDIATE BEHAVIOUR- GIVEN BY
SNEEN –
K1
If k1>k2 then mechanism is SN2, if
• k2> k1 then mechanism is SN1
• Borderline behaviour is found where
the rates of formation and destruction
of the ion pair are of the same order of
magnitude (k1=k2).
SN2
simultaneous
operation
The substrate first ionizes to an
intermediate ion pair that is then
converted to productsR⁺X¯
PRODUCT
•
no intermediate mechanism at all, and
borderline behaviour is caused by
simultaneous operation.
in the same flask, of both the SN1 and
SN2 mechanisms; that is, some
molecules react by the SN1, while
others react by the SN2 mechanism.
• Among the experiments that have been cited for the viewpoint that
borderline behaviour results from simultaneous SN1 and SN2 mechanisms
is the behaviour of 4-methoxybenzyl chloride in 70% aqueous acetone.
4-methoxybenzyl chloride
in 70% aqueous acetone.
conversion to 4-methoxybenzyl
alcohol occurs by an SN1
mechanism.
alcohol is still a product, but now
4-methoxybenzyl azide is another
product.
increases the rate of ionization
but decreases the rate of
hydrolysis, (SN2 MECHANISMFOR AZIDE FORMATION)
The Sni
Mechanism
 (substitution nucleophilic internal)
In a few reactions, nucleophilic
substitution proceeds with retention of
configuration, even where there is no
possibility of a neighboring-group
effect.
Follows second order kinetics
RARE
The reaction between alchols and
thionyl chloride has been studied
exclusively.
Example- α –pehnyl alchol and
thionyl alchol
•It was found that product is formed
with complete retention of
configuration on the starting
alcohol.
•The reaction proceeds with the
formation of a chlorosulphite ester
which collapes with elimination on
SO2.
•The chlorosulphite ester could form
the product by SN2 with inversion,
and SN1 with racemisation.
MECHANISM OF Sni
on the basis of experimental
fact First step- formation of
chlorosulphite
(intermediate).
 Second step- dissociation
of the chlorosulphite
ester to form an ion –pair
(not dissociated).
 Because of the geometry
of the ion pair, the
chlorine atom is forced to
attach the carbonium ion
from the side as original
C-O bond of the alchol
(internal attack).
 If (S)-1-phenyl ethanol and SOCl2 react in presence of a tertiary amine
such as pyridine, the product is (R)-1-phenylethylchloride is obtained, i.e.
Inversion of configuration occurs.
 The pyridine reacts with the HCl, produced in the first step of the
pyridinium hydrochloric acid and Cl¯ being an effective nucleophile,
attacks the alkyl chlorosulphite from the back via SN2 reaction.
 Thus we can say in prescence of pyridine, reaction follows the SN2
mechanism and withoput it follows the SN1 mechanism.
 RATE OF REACTION- both reactant plays crucial role in reaction. Therefore,
RATE= k[ROH] [ SOCL₂].
Nucleophilic
Substitution at an
Allylic Carbon
 Allylic substrates rapidly undergo
nucleophilic substitution reactions .
 usually accompanied by a certain
kind of rearrangement known as an
allylic rearrangement.
When allylic substrates are treated
with nucleophiles under SN1 conditions,
two products are usually obtained: the
normal one and a rearranged one.
• ReasonTwo products are formed because an
allylic type of carbocation is a
resonance Hybrid so that C-1 and C-3
each carry a partial positive charge
and both are attacked by nucleophile
resulting in the formation of two
products:
R-CH=CH-CH₂⁺
•
R-C⁺H-CH=CH₂
This mechanism has been called the
SN1’mechanism.
If equilibrium
reached
stable product
(thermodynamically
controlled product)
Greater
amount
Not
reached
less stable
product
(kinetically
controlled
product)
Greater
amount
• Nucleophilic substitution at an
allylic carbon can also take place
by an SN2 mechanism, in which
case no allylic rearrangement
usually takes place.
• In which the nucleophile attacks
at the γ carbon rather than the
usual position. This mechanism
is called SN2’ mechanism and is
an allylic substitution. The SN2’
mechanism takes place under
SN2 conditions where α
substation sterically retards the
normal SN2 mechanism.
• When a molecule has in an
allylic position a nucleofuge
(leaving group) capable of
giving the SNi reaction, it is
possible for the nucleophile to
attack at γ the position instead
of the a position. This is called
the SNi’ mechanism and has
been demonstrated on 2buten-1-ol and 3-buten-2-ol,
both of which gave 100% allylic
rearrangement when treated
with thionyl chloride in ether.
Ordinary allylic rearrangements
(SN1’) or SN2’ mechanisms
could not be expected to give
100% rearrangement in both
cases.
Nucleophilic Substitution at an Aliphatic
Trigonal Carbon
• The compounds containing a
trigonal carbons, especially
when the carbon is double
bonded to an oxygen, a
sulphur, or a nitrogen undergo
nucleophilic substitution
through tetrahedral
mechanism, often reaction
follows the second order called
addition-elimination.
• In tetrahedral mechanism first
the nucleophile attacks to give
a tetrahedral intermediate and
then the leaving group
departs.
• As expected, this reaction is catalysed by acid because,
protonation decreases the electron density at the carbon
undergoing substitution, which facilitates the attack of
nucleophile:
Nucleophilic Substitution at a Vinylic Carbon
Concerned with the nucleophilic substitution at unsaturated carbon such
as vinylchloride (CH₂=CHCl).
Nucleophilic substitution at a vinylic carbon is difficult under normal
condition and is extremely slow compared to substitution at saturated
carbon. The Vinyl chloride are essentially inert towards nucleophiles.
Reason1. Vinyl C-X bond (x= halogen, oxygen, nitogen) is stronger than the alkyl C-X
bond because of a resonance interaction between the double bonds and an
unsaturated pair on X. This interaction also weakens and polarizes the pi
bond, which is why such compounds are reactive towards the
electophilic addition.
2.
The sn2 transition state as
well as sn1 intermediate (a
vinyl cation) are too high in
energy
to
be
readily
accessible.
• Thus the rate determining step
involves the breaking of C-X bond.
The bond in vinyl halide is harder to
break and reaction is slow.
• After a lot of reserch,
• The vinylic cation can readily made
through by solvolysis of the SN1 kind
if two conditions are met:
1. The leaving group is extremely good
one.
2. The vinylic group contains electron
releasing substituents.
 It takes 16-18 kcal more
energy to break a C-X bond in
vinyl
halide
than
corresponding alkyl halide.
Most commonly used for this purpose is
the super leaving group – trifluro
methanesulfonate
(-OSO2CF3)
WHICH is known as TRIFLATE.
The powerful electron withdrawing F- ATOM( through dispersial of negative
charge) help to stabalise the triflate anion, and makes the parent acid
CF3SO2OH one of the strongest LOWRY- BRONSTED ACID known, much
stronger than known H2SO4 AND HClO4.
REFRENCE1. Advanced organic chemistry: reaction mechanisms and
structure by Jerry March; McGraw Hill
2.Advanced organic chemistry by Dr. Jagdamba singh and Dr.
L.D.S.Yadav; pragati prakshan
3.Organic reactions and their mechanisms ( second edition) by
P.S. KALSI
4. REACTION MECHANISM in organic chemistry by S.M.
Mukhrjee and S.P. Singh and Macmillan.
THANK YOU